Showing papers by "Shahid Beheshti University of Medical Sciences and Health Services published in 2021"

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Abstract: Importance Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count Results Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, −6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48];P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, −∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (Pfor noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%];P = .01). Conclusions and Relevance Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04486508

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.

Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.

Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: results from global burden of disease study 2017

Abstract: Cardiovascular diseases (CVDs) are one of the global leading causes of concern due to the rising prevalence and consequence of mortality and disability with a heavy economic burden. The objective of the current study was to analyze the trend in CVD incidence, mortality, and mortality-to-incidence ratio (MIR) across the world over 28 years. The age-standardized CVD mortality and incidence rates were retrieved from the Global Burden of Disease (GBD) Study 2017 for both genders and different world super regions with available data every year during the period 1990–2017. Additionally, the Human Development Index was sourced from the United Nations Development Programme (UNDP) database for all countries at the same time interval. The marginal modeling approach was implemented to evaluate the mean trend of CVD incidence, mortality, and MIR for 195 countries and separately for developing and developed countries and also clarify the relationship between the indices and Human Development Index (HDI) from 1990 to 2017. The obtained estimates identified that the global mean trend of CVD incidence had an ascending trend until 1996 followed by a descending trend after this year. Nearly all of the countries experienced a significant declining mortality trend from 1990 to 2017. Likewise, the global mean MIR rate had a significant trivial decrement trend with a gentle slope of 0.004 over the time interval. As such, the reduction in incidence and mortality rates for developed countries was significantly faster than developing counterparts in the period 1990–2017 (p < 0.05). Nevertheless, the developing nations had a more rather shallow decrease in MIR compared to developed ones. Generally, the findings of this study revealed that there was an overall downward trend in CVD incidence and mortality rates, while the survival rate of CVD patients was rather stable. These results send a satisfactory message that global effort for controlling the CVD burden was quite successful. Nonetheless, there is an urgent need for more efforts to improve the survival rate of patients and lower the burden of this disease in some areas with an increasing trend of either incidence or mortality.

The prevalence of anxiety and depression among healthcare workers during the COVID-19 pandemic: An umbrella review of meta-analyses.

Abstract: BACKGROUND: Healthcare workers, who are at the forefront of the fight against COVID-19, are particularly susceptible to physical and mental health consequences such as anxiety and depression. The aim of this umbrella review of meta-analyses is to determine the prevalence of anxiety and depression among healthcare workers during the COVID-19 pandemic. METHODS: Using relevant keywords, data resources including PubMed, Scopus, Web of Science, Cochrane, ProQuest, Science Direct, Google Scholar and Embase were searched to obtain systematic reviews and meta-analyses reporting the prevalence of anxiety and depression among healthcare workers during the COVID-19 pandemic from the beginning of January to the end of October 2020. The random effects model was used for meta-analysis, and the I2 index was employed to assess heterogeneity among studies. Data was analyzed using STATA 14 software. RESULTS: In the primary search, 103 studies were identified, and ultimately 7 studies were included in the umbrella review. The results showed that the overall prevalence of anxiety and depression among healthcare workers during the COVID-19 pandemic was 24.94% (95% CI: 21.83-28.05, I2 = 0.0%, P = 0.804) and 24.83% (95% CI: 21.41-28.25, I2 = 0.0%, P = 0.897), respectively. CONCLUSION: This umbrella review shows that the prevalence of anxiety and depression is relatively high among healthcare workers during the COVID-19 pandemic. Healthcare workers should be provided with resources to minimize this risk.

SARS-CoV-2 antibody seroprevalence in the general population and high-risk occupational groups across 18 cities in Iran: a population-based cross-sectional study.

Abstract: Summary Background Rapid increases in cases of COVID-19 were observed in multiple cities in Iran towards the start of the pandemic. However, the true infection rate remains unknown. We aimed to assess the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 18 cities of Iran as an indicator of the infection rate. Methods In this population-based cross-sectional study, we randomly selected and invited study participants from the general population (from lists of people registered with the Iranian electronic health record system or health-care centres) and a high-risk population of individuals likely to have close social contact with SARS-CoV-2-infected individuals through their occupation (from employee lists provided by relevant agencies or companies, such as supermarket chains) across 18 cities in 17 Iranian provinces. Participants were asked questions on their demographic characteristics, medical history, recent COVID-19-related symptoms, and COVID-19-related exposures. Iran Food and Drug Administration-approved Pishtaz Teb SARS-CoV-2 ELISA kits were used to detect SARS-CoV-2-specific IgG and IgM antibodies in blood samples from participants. Seroprevalence was estimated on the basis of ELISA test results and adjusted for population weighting (by age, sex, and city population size) and test performance (according to our independent validation of sensitivity and specificity). Findings From 9181 individuals who were initially contacted between April 17 and June 2, 2020, 243 individuals refused to provide blood samples and 36 did not provide demographic information and were excluded from the analysis. Among the 8902 individuals included in the analysis, 5372 had occupations with a high risk of exposure to SARS-CoV-2 and 3530 were recruited from the general population. The overall population weight-adjusted and test performance-adjusted prevalence of antibody seropositivity in the general population was 17·1% (95% CI 14·6–19·5), implying that 4 265 542 (95% CI 3 659 043–4 887 078) individuals from the 18 cities included were infected by the end of April, 2020. The adjusted seroprevalence of SARS-CoV-2-specific antibodies varied greatly by city, with the highest estimates found in Rasht (72·6% [53·9–92·8]) and Qom (58·5% [37·2–83·9]). The overall population weight-adjusted and test performance-adjusted seroprevalence in the high-risk population was 20·0% (18·5–21·7) and showed little variation between the occupations included. Interpretations Seroprevalence is likely to be much higher than the reported prevalence of COVID-19 based on confirmed COVID-19 cases in Iran. Despite high seroprevalence in a few cities, a large proportion of the population is still uninfected. The potential shortcomings of current public health policies should therefore be identified to prevent future epidemic waves in Iran. Funding Iranian Ministry of Health and Medical Education. Translation For the Farsi translation of the abstract see Supplementary Materials section.

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers

Abstract: The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.

Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series.

Abstract: Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients. A total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases). There were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24–48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48–96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2–7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P < 0.01), IL-8 (P < 0.05), and C-reactive protein (CRP) (P < 0.01) were seen in all six survivors. IL-6 levels decreased in five (P = 0.06) patients and interferon gamma (IFN-γ) levels decreased in four (P = 0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5–19 days (average: 10 days) after the first MSC infusion. A low percentage of lymphocytes (< 10%) and leukocytosis were associated with poor outcome (P = 0.02). All six survivors were well with no complaints of dyspnea on day 60 post-infusion. Radiological parameters of the lung computed tomography (CT) scans showed remarkable signs of recovery. We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.

Burnout among healthcare professionals during COVID-19 pandemic: a cross-sectional study.

Abstract: To describe the prevalence of burnout among healthcare professionals dealing with COVID-19 patients and the associated factors. In this cross-sectional survey, healthcare workers at six university-affiliated hospitals, who had been taking care of COVID-19 patients were studied. Age, gender, marital status, having children, hospital, job category, experience, and work load, as well as the level of burnout in each subscale were measured. 326 persons (53.0%) experienced high levels of burnout. The average score in emotional exhaustion, depersonalization and lack of personal accomplishment was 26.6, 10.2, and 27.3, respectively. The level of burnout in the three subscales varied based on the personal as well as work-related factors and gender was the only variable that was associated with high levels of all three domains. Burnout is prevalent among healthcare workers caring for COVID-19 patients. Age, gender, job category, and site of practice contribute to the level of burnout that the staff experience.

Automated detection of COVID-19 using ensemble of transfer learning with deep convolutional neural network based on CT scans.

Abstract: COVID-19 has infected millions of people worldwide. One of the most important hurdles in controlling the spread of this disease is the inefficiency and lack of medical tests. Computed tomography (CT) scans are promising in providing accurate and fast detection of COVID-19. However, determining COVID-19 requires highly trained radiologists and suffers from inter-observer variability. To remedy these limitations, this paper introduces an automatic methodology based on an ensemble of deep transfer learning for the detection of COVID-19. A total of 15 pre-trained convolutional neural networks (CNNs) architectures: EfficientNets(B0-B5), NasNetLarge, NasNetMobile, InceptionV3, ResNet-50, SeResnet 50, Xception, DenseNet121, ResNext50 and Inception_resnet_v2 are used and then fine-tuned on the target task. After that, we built an ensemble method based on majority voting of the best combination of deep transfer learning outputs to further improve the recognition performance. We have used a publicly available dataset of CT scans, which consists of 349 CT scans labeled as being positive for COVID-19 and 397 negative COVID-19 CT scans that are normal or contain other types of lung diseases. The experimental results indicate that the majority voting of 5 deep transfer learning architecture with EfficientNetB0, EfficientNetB3, EfficientNetB5, Inception_resnet_v2, and Xception has the higher results than the individual transfer learning structure and among the other models based on precision (0.857), recall (0.854) and accuracy (0.85) metrics in diagnosing COVID-19 from CT scans. Our study based on an ensemble deep transfer learning system with different pre-trained CNNs architectures can work well on a publicly available dataset of CT images for the diagnosis of COVID-19 based on CT scans.

The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial.

Abstract: Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19 A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 005) There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19 Further clinical studies are warranted Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020520; URL of trial registry record: https://enirctir/trial/48213

Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment.

Abstract: The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine.

Abstract: Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence.

Abstract: Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules.

Cardiovascular diseases burden in COVID-19: Systematic review and meta-analysis.

Abstract: Background High rate of cardiovascular disease (CVD) have been reported among patients with novel coronavirus disease (COVID-19). Meanwhile there were controversies among different studies about CVD burden in COVID-19 patients. Hence, we aimed to study CVD burden among COVID-19 patients, using a systematic review and meta-analysis. Methods We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs. We have also performed a descriptive meta-analysis on different CVDs. Results Fifty-six studies entered into meta-analysis for ICU admission and mortality outcome and 198 papers for descriptive outcomes, including 159,698 COVID-19 patients. Results of meta-analysis indicated that acute cardiac injury, (OR: 13.29, 95% CI 7.35-24.03), hypertension (OR: 2.60, 95% CI 2.11-3.19), heart Failure (OR: 6.72, 95% CI 3.34-13.52), arrhythmia (OR: 2.75, 95% CI 1.43-5.25), coronary artery disease (OR: 3.78, 95% CI 2.42-5.90), and cardiovascular disease (OR: 2.61, 95% CI 1.89-3.62) were significantly associated with mortality. Arrhythmia (OR: 7.03, 95% CI 2.79-17.69), acute cardiac injury (OR: 15.58, 95% CI 5.15-47.12), coronary heart disease (OR: 2.61, 95% CI 1.09-6.26), cardiovascular disease (OR: 3.11, 95% CI 1.59-6.09), and hypertension (OR: 1.95, 95% CI 1.41-2.68) were also significantly associated with ICU admission in COVID-19 patients. Conclusion Findings of this study revealed a high burden of CVDs among COVID-19 patients, which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.

Prevalence, Deaths, and Disability-Adjusted Life Years Due to Musculoskeletal Disorders for 195 Countries and Territories 1990–2017

Abstract: Objective To report the levels and trends of prevalence, deaths, and disability‐adjusted life years (DALYs) due to musculoskeletal disorders, categorized as low back pain, neck pain, osteoarthritis (OA), rheumatoid arthritis (RA), gout, and other musculoskeletal disorders, across 195 countries and territories from 1990 to 2017 according to age, sex, and Sociodemographic Index (SDI; a composite of sociodemographic factors). Methods Data were obtained from the Global Burden of Disease (GBD) Study 2017. The fatal and nonfatal burdens of musculoskeletal disorders were estimated using the Cause of Death Ensemble model and Bayesian meta‐regression tool, respectively. Estimates were provided for all musculoskeletal disorders and the corresponding 6 categories at global, regional, and national levels from 1990 to 2017. Counts and age‐standardized rates per 100,000 population along with 95% uncertainty intervals (95% UIs) were reported for prevalence, deaths, and DALYs. Results Globally, there were ~1.3 billion prevalent cases (95% UI 1.2 billion, 1.4 billion), 121.3 thousand deaths (95% UI 105.6 thousand, 126.2 thousand), and 138.7 million DALYs (95% UI 101.9 million, 182.6 million) due to musculoskeletal disorders in 2017. Age‐standardized prevalence, death, and DALY rates per 100,000 population were 16,276.2 (95% UI 15,495.5, 17,145.8), 1.6 (95% UI 1.4, 1.6), and 1,720 (95% UI 1,264.4, 2,259.2), respectively. Age‐standardized prevalence (−1.6% [95% UI −2.4, −0.8]) and DALY rates (−3.5% [95% UI −4.7, −2.3]) decreased slightly from 1990. The global point prevalence rate of musculoskeletal disorders in 2017 was higher in women than in men and increased with age up to the oldest age group. Globally, the proportion of prevalent cases according to category of musculoskeletal disorders in 2017 was greatest for low back pain (36.8%), followed by other musculoskeletal disorders (21.5%), OA (19.3%), neck pain (18.4%), gout (2.6%), and RA (1.3%). These proportions did not change appreciably compared with 1990. The burden due to musculoskeletal conditions was higher in developed countries. The countries with the highest age‐standardized prevalence rates of musculoskeletal disorders in 2017 were Switzerland (23,346.0 [95% UI 22,392.6, 24,329.8]), Chile (23,007.9 [95% UI 21,746.5, 24,165.8]), and Denmark (22,166.1 [95% UI 20,817.2, 23,542.1]). The greatest increases from 1990 were found in Chile (10.8% [95% UI 6.6, 15.4]), Benin (8.8% [95% UI 6.7, 11.1]), and El Salvador (8.5% [95% UI 5.5, 11.9]). Conclusion There is a large burden of musculoskeletal disorders globally, with some notable inter‐country variation. Some countries have twice the burden of other countries. Increasing population awareness regarding risk factors, consequences, and evidence‐informed treatment strategies for musculoskeletal disorders with a focus on the older female population in developed countries is needed, particularly for low back and neck pain and OA, which contribute a large burden among this cohort.

Rhino-orbital mucormycosis during steroid therapy in COVID-19 patients: A case report.

Abstract: Purpose:To report two cases of COVID-19 under treatment with a corticosteroid; in one case rhino-orbitocerebral mucormycosis and in another one rhino-orbital mucormycosis developed.Case presentatio...

Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.

Abstract: PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

Phytosterols: From Preclinical Evidence to Potential Clinical Applications.

Abstract: Phytosterols (PSs) are plant-originated steroids. Over 250 PSs have been isolated, and each plant species contains a characteristic phytosterol composition. A wide number of studies have reported remarkable pharmacological effects of PSs, acting as chemo-preventive, anti-inflammatory, antioxidant, antidiabetic, and anti-atherosclerotic agents. However, PS bioavailability is a key issue, as it can be influenced by several factors (type, source, processing, preparation, delivery method, food matrix, dose, time of administration into the body, and genetic factors), and the existence of a close relationship between their chemical structures (e.g., saturation degree and side chain length) and low absorption rates has been stated. In this sense, the present review intends to provide in-depth data on PS therapeutic potential for human health, also emphasizing their pre-clinical effects and bioavailability-related issues.

Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.

Abstract: As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.

Systematic Review and Meta-Analysis of Fear of COVID-19

Abstract: Background: Due to lack of preparedness of health systems, fast spread of the new virus, high mortality rates, and lack of a definite treatment, the outbreak of Coronavirus disease (COVID-19) led to high levels of fear and anxiety in different populations. In addition, isolation, mental disorders, and limitations in social interactions as a result of lockdown and travel ban increased the fear of the new coronavirus. Methods: International databases, including Scopus, PubMed, Web of Science, and Google scholar, were searched without any time limitation, and all observational studies published in English reporting the mean of fear of COVID-19 based on the Fear of COVID-19 scale (FCV-19S) were included in the analysis. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Random effects model, subgroup analysis, and meta-regression analysis were used to analyze the data. Heterogeneity across studies was examined using Cochran's Q test and I2 statistic. All the statistical analyses were conducted using R software v4.0.3. Results: A total of 44 articles with a sample size of 52,462 were reviewed. A pooled mean of 18.57 was found for fear of COVID-19. The mean of fear of COVID-19 was higher in women than in men (20.67 vs. 18.21). The highest and lowest means of fear of COVID-19 had been found in Asia (18.36) and Australia (17.43) based on continent, and in hospital staff (19.51) and college students (17.95) based on target population, respectively. In addition, the highest and lowest means of fear of COVID-19 were related to items #1 and #3 of the scale, respectively. According to the results of meta-regression analysis, there was no significant association between the mean of fear of COVID-19 and sample size and participants' age. In addition, publication error was not significant (P = 0.721). Conclusion: The mean of fear of COVID-19 was high around the world; therefore, it seems necessary to pay more attention to the negative effects of the COVID-19 pandemic on mental health.

Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.

Abstract: Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10–5.17, P-value = 0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63–3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies. Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.

Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits.

Abstract: Genistein is an isoflavone first isolated from the brooming plant Dyer’s Genista tinctoria L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword “genistein” from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.

Deep Learning in the Detection and Diagnosis of COVID-19 Using Radiology Modalities: A Systematic Review.

Abstract: Introduction: The early detection and diagnosis of COVID-19 and the accurate separation of non-COVID-19 cases at the lowest cost and in the early stages of the disease are among the main challenges in the current COVID-19 pandemic. Concerning the novelty of the disease, diagnostic methods based on radiological images suffer from shortcomings despite their many applications in diagnostic centers. Accordingly, medical and computer researchers tend to use machine-learning models to analyze radiology images. Material and Methods. The present systematic review was conducted by searching the three databases of PubMed, Scopus, and Web of Science from November 1, 2019, to July 20, 2020, based on a search strategy. A total of 168 articles were extracted and, by applying the inclusion and exclusion criteria, 37 articles were selected as the research population. Result: This review study provides an overview of the current state of all models for the detection and diagnosis of COVID-19 through radiology modalities and their processing based on deep learning. According to the findings, deep learning-based models have an extraordinary capacity to offer an accurate and efficient system for the detection and diagnosis of COVID-19, the use of which in the processing of modalities would lead to a significant increase in sensitivity and specificity values. Conclusion: The application of deep learning in the field of COVID-19 radiologic image processing reduces false-positive and negative errors in the detection and diagnosis of this disease and offers a unique opportunity to provide fast, cheap, and safe diagnostic services to patients.

Major depressive disorder diagnosis based on effective connectivity in EEG signals: a convolutional neural network and long short-term memory approach

Abstract: Deep learning techniques have recently made considerable advances in the field of artificial intelligence. These methodologies can assist psychologists in early diagnosis of mental disorders and preventing severe trauma. Major Depression Disorder (MDD) is a common and serious medical condition whose exact manifestations are not fully understood. So, early discovery of MDD patients helps to cure or limit the adverse effects. Electroencephalogram (EEG) is prominently used to study brain diseases such as MDD due to having high temporal resolution information, and being a noninvasive, inexpensive and portable method. This paper has proposed an EEG-based deep learning framework that automatically discriminates MDD patients from healthy controls. First, the relationships among EEG channels in the form of effective brain connectivity analysis are extracted by Generalized Partial Directed Coherence (GPDC) and Direct directed transfer function (dDTF) methods. A novel combination of sixteen connectivity methods (GPDC and dDTF in eight frequency bands) was used to construct an image for each individual. Finally, the constructed images of EEG signals are applied to the five different deep learning architectures. The first and second algorithms were based on one and two-dimensional convolutional neural network (1DCNN-2DCNN). The third method is based on long short-term memory (LSTM) model, while the fourth and fifth algorithms utilized a combination of CNN with LSTM model namely, 1DCNN-LSTM and 2DCNN-LSTM. The proposed deep learning architectures automatically learn patterns in the constructed image of the EEG signals. The efficiency of the proposed algorithms is evaluated on resting state EEG data obtained from 30 healthy subjects and 34 MDD patients. The experiments show that the 1DCNN-LSTM applied on constructed image of effective connectivity achieves best results with accuracy of 99.24% due to specific architecture which captures the presence of spatial and temporal relations in the brain connectivity. The proposed method as a diagnostic tool is able to help clinicians for diagnosing the MDD patients for early diagnosis and treatment.

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy

Abstract: Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent.